Aggressive periodontitis (AgP) is a group of rare, but severe, rapidly progressing form of periodontitis, characterized by an early age of onset and rapid bone destruction that leads to early tooth loss. It appears that this disease result from a combination of bacterial infection and hyperactivity of the immune system. However, given its rare occurrence and difficulties in gathering large populations, knowledge on specific mechanisms and consequently proper treatment of this disease remains based on case reports and a few small clinical trials. We have identified a cohort of at least fifty African-American children diagnosed within one clinical setting in Tallahassee, Florida, with a very similar pattern of localized AgP (LAgP). This group represents a small underserved population of north Florida. Our preliminary data shows an exacerbated immune response and specific groups of bacteria involved with this disease. With proper diagnostic tools and with the knowledge we have already gained within this population, we believe we are able to gather a larger population to further understand this aggressive disease and the effects conventional treatment has upon its mechanisms. Therefore, the overall goal of this study is to determine which mechanisms are responsible for the rapid tissue destruction in children with aggressive periodontitis, and how conventional periodontal intervention affects these mechanisms. Our central hypothesis is that AgP is associated with a combination of a hyper- inflammatory innate trait and a specific group of bacteria and that periodontal therapy is able to modulate these parameters responsible for tissue destruction. In order to test our hypothesis we propose to: 1- To determine if 'traditional' periodontal treatment alters the hyper-responsive trait observed in LAgP by evaluating the systemic regulatory mechanisms of cyto/chemokine expression which contribute to tissue destruction; 2- To determine how local inflammatory mediators and metalloproteinases are modulated through the progression and treatment of periodontal disease in children with LAgP.; and 3- To determine alterations in subgingival microflora associated with LAgP after traditional periodontal treatment. We hope that the outcomes of this study will provide us with a better understanding of the mechanisms involved with aggressive periodontal tissue destruction in children and how treatment affects these mechanisms. This will enables us to investigate early and improved treatment approaches to prevent early tooth loss and possible future systemic complications. PUBLIC HEALTH RELEVANCE: Although of low prevalence, aggressive periodontitis is a rapid destructive form of periodontal disease that initiates at a young age, leading to premature loss of first molars and incisors. Little is known on the mechanisms of this disease. It is imperative to understand mechanisms of disease to establish proper treatment. We have established a controlled study in a homogeneous population presenting similar aggressive disease characteristics to evaluate the mechanisms of this disease longitudinally. It is the goal of this study to determine immunological and microbiological mechanisms responsible for the rapid tissue destruction in children with localized aggressive periodontitis and how conventional periodontal intervention affects these mechanisms. Important knowledge gained with this proposal will aid in defining specific treatment approaches to better control disease progression and prevent disease initiation in susceptible individuals.